Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction

Graft-versus-host disease (GVHD) is the major complication after allogeneic hemopoietic stem cell transplantation. GVHD is destructive by itself and sets the stage for other sequelae, in particular, overwhelming infections. Recent investigations have improved our understanding of the underlying pathophysiology of GVHD. There are now compelling data on the role of host tissue destruction as the initial insult, extensive interactions of cellular donor and host components, a complex network of cytokines, adhesion molecules, and other components in the development of GVHD. The improved understanding of interactions among various signals is likely to allow for the development of new prophylactic strategies. A review of the data shows, however, that results are very dependent upon the models used. It is difficult or impossible to separate completely the discussion of cytokines that affect hemopoietic cells from discussion of cytokines that exert effects on immune cells. Furthermore, secondary effects on immune cells via hemopoietic cells complicate the picture. Application of the principles of cytokine signaling to the clinical setting may necessitate new trial design structures that take into consideration donor and host characteristics as well as the kinetics of GVHD development.